Nanospherical Ceramics: Resisting Bacteria Infection. While increasing bone cell functions, nanomaterials reduce bacteria functions. S.

Transcription

1 Nanospherical Ceramics: Resisting Bacteria Infection While increasing bone cell functions, nanomaterials reduce bacteria functions. S. Epidermis Conventional ZnO Positive Control (Wrought Ti) Nanophase ZnO Conventional ZnO Mag. = 400X Nanophase ZnO

2 Angstrom Medica: Bilateral Canine Osseointegration Distal and Proximal Femur 2 weeks Bone Bonding 4 weeks NanOss HA Conventional HA Titanium Stainless Steel Polymers 2 weeks 8-12 weeks weeks weeks Does not bond

3 Osseointegration at 4 weeks Distal Femur 2 mm

4 Histology Sections of Nanophase Alumina Implanted Into Neonatal Rat Calvaria Soft Fibrous Tissue Alumina/ PLGA New Bone Alumina 24 nm (nanophase) grain size alumina 177 nm (conventional) grain size alumina with PLGA Implantation time: 8 weeks. Stain: H & E.

5 COATINGS Nanospherical Ceramics Uncoated Ta Scaffolds Conventional HA Coated Ta Nano HA Coated Ta Working in collaboration with Spire Biomedical, using their IonTiteTM technology, we have coated traditional orthopedic implant materials with nanospherical ceramics to increase bone growth. Ta Scaffold

6 COATINGS Nanospherical Ceramics Implantation Time = 2 weeks; Animal Model = rat calvaria Uncoated Ta Scaffolds Nano HA Coated Ta Conventional HA Coated Ta

7 PART I (cont.) BONE: Nano-fiber Ceramics Materials Research Society Bulletin, December 2003.

8 Bone is a Nano-fibered Material Collagen Fibers: composed of Type I collagen which is a triple helix 300 nm in length; 0.5 nm in width; and periodicity of 67 nm Cancellous Bone Osteoclast Cancellous Bone Osteoblast Osteocyte Compact Bone Lamella Hydroxyapatite Crystals: less than 50 nm in length and 5 nm in diameter Capillary Capillary Osteocyte Redrawn and adapted from Fung Biomechanics: Mechanical Properties of Living Tissue, Springer-Verlag, New York, 1993 and Keaveny and Hayes, Bone 7:285, 1993.

9 Nanofiber Ceramic Synthesis Electro-explosion of aluminum is used to create 100 nm aluminum particles. A microsecond pulse of J is applied to an aluminum wire. The wire explodes when the pulse is discontinued. The exploded fragments pass through an argon environment and become quenched. These particles are digested in water to create an aluminum oxide Al(OH)3 sol-gel. Subsequent drying of this material (to 400º C) leaves an alumina nano-fiber. Argon Environment Aluminum Particles Alumina Nanofibers Sol-Gel Heat Aluminum Wire High-current, HighVoltage Microsecond Pulse From T. J. Webster, in Nanostructured Biomaterials (H.S. Nalwa, editor), American Scientific Publishers, in press, 2005.

10 Design of Nano-fiber Ceramics for Orthopedic Implants TEM of Individual Alumina Nano-dimensional Fibers Bar = 100 nm (left) and 20 nm (right). R.L. Price, K. M. Haberstroh, and T.J. Webster, Enhanced functions of osteoblasts on nanostructured surfaces of carbon and alumina, Medical and Biological Engineering and Computing 41: (2003).

11 High Magnification Scanning Electron Micrographs of Alumina Substrates Conventional Alumina Nano-spherical Alumina Nano-fiber Alumina Original Magnification = 10,000X; Bar = 1 m. R.L. Price, L.G. Gutwein, L. Kaledin, F. Tepper, and T.J. Webster, Journal of Biomedical Materials Research 67A: (2003).

12 Enhanced Osteoblast Adhesion on Nano-fiber Alumina * ** 2000 * Cell Density (cells/square cm) Glass Titanium (reference) 3 HA Conven-NanoNanotional spherical fiber Alumina Compact Culture medium = DMEM supplemented with 10% fetal bovine serum. Seeding density = 2,500 cells/cm2. Culture time = 2 hrs. Values are mean +/- SEM; n = 3; * p < 0.01 (compared to titanium); ** p < 0.05 (compared to nano-spherical alumina). R.L. Price, L.G. Gutwein, L. Kaledin, F. Tepper, and T.J. Webster, Journal of Biomedical Materials Research 67A: (2003).

13 Other Novel Nano-Formulations of Alumina Nanoporous Alumina Osteoblast filipodia Studies have shown superior osteoblast functions leading to increased in vitro new bone synthesis on nano-porous alumina. Osteoblast filipodia Nanoporous Alumina Karlsson et al, Biomaterials 24 (2003)

14 PART I (cont.) BONE: Carbon Nanofibers Science News, January 24, p. 62, 2004.

15 Carbon Nanofiber Synthesis Chemical Vapor Deposition A metal catalyst acts as a template for carbon deposition from a hydrocarbon gas environment. More time in the hydrocarbon environment = larger fiber diameter. Carbon Nanofiber Metal Catalyst 100 nm J. U. Ejiofor, M. C. Waid, J. L. McKenzie, R. L. Price, and T. J. Webster, Nanotechnology 15:48-54 (2004).

16 Design of Carbon Nanofibers for Orthopedic Implants pyrolytic outer core Fiber Fiber Diameter (nm) Surface Energy Nanophase w/ pyrolytic outer core 100 Low Conventional w/ pyrolytic outer core 200 Low Nanophase w/o pyrolytic outer core 60 High Conventional w/o pyrolytic outer core 125 High K. L. Elias, R. L. Price, and T. J. Webster, Biomaterials 23: (2002). no pyrolytic outer core Figure: TEM of Individual Carbon Nano-dimensional Fibers Bar = 100 nm.

17 Scanning Electron Micrographs of Carbon Fiber Compacts Nanophase w/low Surface Energy Conventional w/low Surface Energy Bar = 1 m. Nanophase w/high Surface Energy Conventional w/high Surface Energy R. L. Price, M. C. Waid, K. M. Haberstroh, and T. J. Webster, Increased, select bone cell adhesion on formulations containing carbon nanofibers, Biomaterials, 24(11): , 2003.

18 Enhanced, Select Osteoblast Adhesion on Carbon Nanofibers 2500 Cell Density (cells/square cm) Osteoblasts Smooth Muscle Cells Fibroblasts Chondrocytes * * Etched Glass Conventional w/ low surface energy Conventional w/ high surface energy Nanophase w/ high surface energy Nanophase w/ low surface energy Carbon Nanofibers Values are mean +/-SEM; n=3; * p<0.10 (compared to conventional counterpart). R. L. Price, M. C. Waid, K. M. Haberstroh, and T. J. Webster, Biomaterials, 24(11): , 2003.

19 Enhanced Adhesion Translates into Increased Subsequent Functions Stages of Osteoblast Differentiation Proliferation and extracellular matrix synthesis OSTEOBLAST PROLIFERATION Extracellular matrix development and maturation OSTEOBLAST DIFFERENTIATION Synthesis of : Type I collagen Fibronectin Vitronectin 0 Extracellular matrix mineralization Synthesis of : Osteopontin Alkaline phosphatase Collagenase 12 Synthesis of : Osteocalcin Bone sialoprotein 21 Days in Culture T. J. Webster, in Advances in Chemical Engineering Vol. 27, Academic Press, NY, pgs , 2001.